PubMed Health⌕ Search

Biomedical subjects

F Akiyama

Publications and source records attributed to F Akiyama.

At least 19 recordsLinked to original sources
PubMed2005

Update results of FEC followed by docetaxel neoadjuvant trials for primary breast cancer.

This study has been initiated to evaluate the safety, clinical and pathologic response as well as the relation of response (pCR or non-pCR) and survival (overall and relapse-free) of fluorouracil, epirubicin and cyclophosphamide (FEC) followed by docetaxel (DOC) as preoperative chemotherapy in patients with operable breast cancer. Japanese patients with primary breast cancer, Tlc-3N0M0 or T1-3NIM0, age 20-60, PS 0-1 were included in this study. Preoperative chemotherapy consisted of 4 cycles of FEC (500 mg/m(2), 100 mg/m(2), 500 mg/m(2)) every 3 weeks followed by 4 cycles of DOC (75 mg/m(2)) every 3 weeks. Since June 2002, 200 patients were enrolled in this study, and the time of this interim analysis, 80 patients were evaluable for safety and clinical efficacy. The overall clinical response rate was 71.4% (14% CR, 44% PR, 42% SD/PD), and the only G3,4 toxicities, neutropenia and febrile neutropenia were observed in 54% and 14% of patients, respectively. Eighty nine patients were evaluable for pathologic response by central review. Pathologic response was evaluated among invasive tumors on multiple cross-section specimens based on a modified version of the Japanese grading system for Japanese Breast Cancer Society. The pathologic response rate was 17%. In this ongoing trial, FEC followed by DOC was active and well tolerated.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Unargued issues on the pathological assessment of response in primary systemic therapy for breast cancer.

PURPOSE: The role of primary systemic therapy (PST) in the treatment of operable breast cancer is currently under intensive investigation in the hope of allowing greater conservation of the breast, and emerging evidence suggests that induction of a pathological complete response (pCR) is at least, to some extent, predictive of long-term clinical response. In this review, we highlight the issues of pathologic evaluation after PST. METHODS: We performed a computer-assisted MEDLINE search, and additional references were found in the bibliographies of these articles. RESULTS: So far, several grading classifications are used to assess pathologic responses after PST, and pCR rates vary from 1% to 54.7% according to the PST regimens employed. However, the term "pCR" has not been applied in a consistent, standardized manner, and the pCR rates appear to depend not only on the differences in the definition of pCR, but also on the extent of tissue sampling and the techniques used for pathologic examination. So far, only limited information is available about the reliability and validity of the definition of pathologic responses. CONCLUSION: Assessment of pCR needs to be standardized, and each grading system should be verified for reliability and validity. As a lack of standard for tumor processing and evaluation may result in considerable fluctuation of pCR rates between trials, we should take into account the differences in the definition of pathologic response when comparing the results of PST.

Breast Neoplasms↗
PubMed2005

Expression of GCDFP-15 and AR decreases in larger or node-positive apocrine carcinomas of the breast.

AIMS: Apocrine carcinoma of the breast is typically, though not always, positive for gross cystic disease fluid protein-15 (GCDFP-15). In order to clarify the clinical significance of GCDFP-15 in apocrine carcinomas, GCDFP-15 expression was examined in apocrine carcinomas of different stages and compared with clinicopathological factors. Apocrine lesions reportedly exhibit an unusual immunohistochemical status, expressing androgen receptors (AR) instead of oestrogen receptors (ER), progesterone receptors (PR), or bcl-2. Their expression was also examined. METHODS AND RESULTS: Fifty-two apocrine carcinomas were examined immunohistochemically. Thirty-nine (75%) and 29 (56%) were positive for GCDFP-15 and AR, respectively. GCDFP-15 positivity was significantly lower in infiltrating carcinomas than intraductal carcinomas (P = 0.0111). In infiltrating carcinomas, GCDFP-15 positivity was significantly low in tumours > or = 15 mm (P = 0.0005) and node-positive tumours (P = 0.0004). Similar phenomena were observed for AR. Rare cases were positive for ER (3.8%), PR (5.8%), and bcl-2 (1.9%). CONCLUSIONS: GCDFP-15 positivity is transient and should not be considered a definitive marker of apocrine carcinomas. Cases which have apocrine features but lack GCDFP-15 expression should rather be considered as advanced apocrine carcinomas. ER/PR/bcl-2 negativity will sometimes be helpful to confirm the diagnosis of apocrine carcinoma, because it is more consistent than GCDFP-15/AR positivity.

Adult↗
PubMed2004

Transforming growth factor-beta1 gene polymorphism modifies the histological and clinical manifestations in Japanese patients with IgA nephropathy.

Transforming growth factor (TGF)-beta1, a multifunctional cytokine, which regulates proliferation and differentiation of a variety of cell types, has the central role in the development and progression of renal injury in both animal models and human. Although it has been suggested that genetic variations in the TGF-beta1 gene are associated with the activity of the gene product, their clinical significance in glomerular disease is unknown. We investigated whether the polymorphisms of C-509T and T869C in TGF-beta1 account for interindividual variation in manifestations of IgA nephropathy (IgAN) using 626 Japanese subjects including 329 patients with histologically proven IgAN and 297 healthy controls with normal urinalysis. The frequencies of genotypes, alleles, and major haplotypes were similar between the patients and controls. The C-509T and T869C polymorphisms were in tight linkage disequilibrium, and the major haplotypes were C-C and T-T, which accounted for more than 95% of the total. In patients with -509CC and in those with the 869CC, urinary protein excretion was higher than in those with other genotypes, whereas no difference in other clinical manifestations was noted. Moreover, patients with -509CC and those with 869CC genotypes presented with a significant higher score of mesangial cell proliferation than in those with other genotypes. These results suggest that TGF-beta1 gene polymorphisms are specifically associated with heavy proteinuria and mesangial cell proliferation in Japanese patients with IgAN, although they do not confer susceptibility to this disease.

Adult↗
PubMed2003

Breast carcinoma in women over the age of 85: distinct histological pattern and androgen, oestrogen, and progesterone receptor status.

AIMS: The pathogenesis of breast carcinoma in very elderly women is of interest, because oestrogen levels are likely to be extremely low during the development of the disease. In an effort to understand the pathogenesis of breast carcinoma in these women, this study was undertaken to compare the histological patterns and hormone receptor status of breast carcinomas arising in very elderly and younger women. METHODS AND RESULTS: Thirty-seven breast carcinomas from women over the age of 85 years at the time of their operation were examined histologically and compared with those from a large group of premenopausal women. The proportions of mucinous carcinoma and apocrine carcinoma were significantly greater in older women. The expression of steroid hormone receptors was studied immunohistochemically. Androgen receptor-positive carcinomas were significantly more frequent among older women, whereas progesterone receptor-positive carcinomas were significantly less frequent. There was no statistically significant difference in oestrogen receptor-alpha or -beta expression between the tumours from both groups. CONCLUSION: Breast carcinomas in women over the age of 85 years have a different morphological spectrum from carcinomas in younger age groups and may have different pathogenesis mechanisms that may be more dependent on androgen and androgen receptor interaction. Differences from the results of the other studies are discussed.

Adenocarcinoma↗
PubMed2002

Breast conserving treatment without radiotherapy.

Radiotherapy (RT) is not always necessary for the prevention of ipsilateral breast recurrence in cases where cancer is not detected in the remaining breast tissue after breast conserving surgery. In addition, under these circumstances, the rate of a second primary cancer of the remaining breast is theoretically equal to the rate of contralateral breast cancer. In performing breast conserving treatment (BCT) at our institution we do not treat with RT if a strict serial pathological examination of the specimen (every 5 mm) reveals that the case has been safely resected (negative surgical margins). From 1986 to 1998, 827 patients (157 were ductal carcinoma in situ, and 670 were invasive) underwent BCT without RT at the Cancer Institute Hospital. Ipsilateral breast cancer was observed in 46 cases or 5.6% (0.85% annually) during a median observation period of 67 months. Of these 46 cases, 19 (2.3%) were diagnosed as a recurrence and 27 cases (3.3%) were second primary cancers. This recurrence rate is equivalent to the rate observed in 406 cases of BCT (1.7%) that were treated with RT. Most of these cases had shown positive surgical margins. Furthermore, the rate of occurrence of second cancers is not significantly different from the rate of occurrence of contralateral breast cancers. These results suggest that, by selecting irradiation cases based on careful pathological examinations, BCT can be safely performed.

Breast Neoplasms↗
PubMed2001

Detection of HER-2/neu (c-erb B-2) DNA amplification in primary breast carcinoma. Interobserver reproducibility and correlation with immunohistochemical HER-2 overexpression.

BACKGROUND: Fluorescent in situ hybridization (FISH) has been shown to be one of the most reliable methods with which to estimate the status of the HER-2/neu (or c-erb B-2) oncogene at the DNA level. METHODS: To study interobserver reproducibility and to determine more clinically correlated criteria for HER-2/neu alterations, two observers independently estimated HER-2/neu DNA status. The correlation between the consensus HER-2/neu DNA status by FISH and HER-2/neu protein status detected by immunohistochemistry (IHC) using a polyclonal antibody was studied in 216 surgically resected breast carcinomas and 34 noncancerous tissues. RESULTS: According to the HER-2/CEP17 ratio and mean HER-2 copies per nucleus, agreement level of HER-2/neu amplification was shown to be nearly perfect between two observers (kappa statistic (kappa) = 0.94 and kappa = 0.84). Finally, 40 tumors (19%) were judged to have HER-2/neu DNA amplification, with 6 having low-level amplification (> or = 2 but < 3 folds) and 34 having high-level amplification (> or = 3 folds). One hundred seventy-six other tumors, including 3 tumors that only 1 of the observers determined to be low-level amplifiers, and 34 noncancerous tissues had no detected amplification. The DNA amplification status was concordant between invasive and intraductal components in 14 carcinomas. HER-2/neu protein overexpression of moderate (2+) or high (3+) intensity based on IHC was detected in 51 carcinomas (24%), and was 2+ in 20 carcinomas and 3+ in 31 carcinomas. The HER-2/CEP17 ratio of > or = 2 was concordant with IHC findings of 2+/3+ in 91% of carcinomas (195 of 215 carcinomas), with a sensitivity of 70% (35 of 50 carcinomas) and a specificity of 97% (160 of 165 carcinomas). High-level amplification was detected in 29 of 31 IHC 3+ cases (94%), but in only 5 of 20 IHC 2+ cases (25%) and 0 in 165 IHC 0/1+ cases. All 34 cases with high-level amplification showed an IHC score of 3+ (29 cases) or an IHC score of 2+ (5 cases), but only 1 case was found to have an IHC score of 3+ and the remainder were IHC 0/1+ in 6 low-amplification cases. The concordance rate of the high-level amplification with an IHC score of 3+ was 97% (208 of 215 cases), with a sensitivity of 94% (29 of 31 cases) and a specificity of 97% (179 of 184 cases). CONCLUSIONS: The results of the current study indicated that high-level HER-2/neu amplification and an IHC score of 3+ nearly optimally identified breast carcinomas with clinically and biologically significant HER-2/neu activation. Conversely, it was confirmed that careful interpretation of test results is required in the case of low-level amplification and/or an IHC score of 2+.

Breast Neoplasms↗
PubMed2001

Is the UICC pathological node status system useful? Comparison with the Japanese Breast Cancer Society pathological node status system.

BACKGROUND AND OBJECTIVES: The UICC and the Japanese Breast Cancer Society have different TNM classifications. There is a large discrepancy between the pathological node status in the UICC (UICC-NS) and JBCS (JBCS-NS) systems. We compared the UICC-NS with the JBCS-NS. METHODS: Reviewed were data on 1,684 invasive ductal carcinomas at the Cancer Institute Hospital from 1981 to 1986. Each case was categorized according to the UICC-NS and JBCS-NS, respectively. Overall survival 10 years after surgery (OS) by UICC-NS and JBCS-NS was calculated by the Kaplan-Meier method. RESULTS: OS with UICC-NS and number of case were, respectively, 87.8% and 968 for pN0, 83.9% and 93 for pN1a, 71.6% and 190 for pN1bi, 60.0% and 25 for pN2, 58.8% and 51 for pN1bii, 55.7% and 238 for pN1biii, 54.2% and 24 for pN1biv, 44.8% and 58 for pN3, and 20.6% and 34 for pM (LYM). Differences between pN1a and pN1bi and pN3 and pM (LYM) were significant (p < 0.05). In JBCS-NS, they were 87.8% and 968 for n0, 75.3% and 384 for n1 alpha, 51.3% and 152 for n1 beta, 46.6% and 141 for n2, 21.2% and 33 for n3, 0% and 2 for n4d and n4i, respectively. Differences between n0 and n1 alpha, n1 alpha and n1 beta, and n2 and n3 were significant (p < 0.05). CONCLUSIONS: With a large number of classification factors, UICC-NS was more complicated and hard to show significant difference in OS than JBCS-NS. But the latter also had redundant classifications. So, it is necessary to establish a new, simple, and easy-to-register node classification in future.

Adult↗
PubMed2001

Is the invasion depth in millimeters valid to determine the prognosis of early invasive cervical adenocarcinoma? A case of recurrent FIGO stage IA1 cervical adenocarcinoma.

BACKGROUND: Recurrence of FIGO stage IA1 cervical adenocarcinoma is extremely rare. We herein report a patient with early invasive cervical adenocarcinoma who developed a recurrence in the vaginal stump. CASE: A 52-year-old female complained of contact bleeding. Biopsy of the uterine cervix verified cervical adenocarcinoma, and the patient underwent Okabayashi hysterectomy with pelvic lymphadnectomy and bilateral adnectomy. Histopathologic examination of the uterus revealed an invasive cancer 3 mm in depth. Neither lymph node metastasis nor lymph-vascular space invasion was observed. However, the depth of her normal cervical gland area was 2 mm only, and the cancer invasion involved an area which was deeper than the normal cervical gland area. The vaginal stump recurrence developed 4 years after surgery. CONCLUSION: The depth of invasion with reference to that of normal cervical glands may become a possible prognostic factor for early invasive cervical adenocarcinoma.

Adenocarcinoma↗
PubMed2001

Three-dimensional MR imaging of mammographically detected suspicious microcalcifications.

BACKGROUND: The purpose of this study was to evaluate the diagnostic value and clinical significance of three-dimensional MR imaging of the breast in patients with mammographically detected suspicious microcalcifications. METHODS: Forty patients with suspicious microcalcifications on mammography were evaluated with three-dimensional MR imaging. MR findings were grouped mainly by distribution of abnormal enhancement (linear, focal-clumped, segmental-clumped, segmental-stippled and diffuse-stippled). These findings were compared with the mammography findings according to the criteria of the Breast Imaging Reporting and Data System (BI-RADS) and histopathologic data. RESULTS: Twenty patients had proven malignancies, most frequently ductal carcinoma in situ. For all the cases, linear (100%) and segmental-clumped type (100%) enhancement on MR imaging showed a significantly higher risk for malignancy. Diffuse stippled type (7%) and no enhancement (0%) on MR imaging indicated the lowest possibility of malignancy. 3D-MR imaging showed a sensitivity of 90%, a specificity of 95% and an overall accuracy of 93% in this study. CONCLUSIONS: Three-dimensional MR imaging of the breast can more accurately diagnose ductal carcinoma in situ. Combined with mammography, this procedure is useful for reducing the number of false-positive biopsies and helpful for deciding the better management of patients with mammographically detected suspicious microcalcifications.

Adult↗
PubMed2001

Evaluation of HER2 status: for the treatment of metastatic breast cancers by humanized anti-HER2 Monoclonal antibody (trastuzumab) (Pathological committee for optimal use of trastuzumab).

For the treatment of patients with metastatic breast cancer by humanized anti- human epidermal growth factor receptor type 2 (HER2) antibody (trastuzumab), it is important to evaluate HER2 status adequately. "A guideline for HER2 testing" and "HER2 atlas" produced by the "Pathological committee for optimal use of trastuzumab" are introduced in this report. Appropriate evaluations of biological markers are essential for targeting therapy.

Antibodies, Monoclonal↗
PubMed2001

Association of allelic losses at 3p25.1, 13q12, or 17p13.3 with poor prognosis in breast cancers with lymph node metastasis.

To identify specific allelic losses that might correlate with postoperative mortality of patients with node-positive breast carcinomas, we examined tumors from a cohort of 263 such patients, who were followed clinically for 5 years postoperatively, for allelic losses among 18 microsatellite markers. Patients whose tumors had lost an allele at 3p25.1, 13q12, or 17p13.3 had significantly higher risks of mortality than those whose tumors retained both alleles at those loci. At 3p25.1, the 5-year mortality rate was 33.8% among patients with losses vs. 16.8% with retention (P = 0.0154); at 13q12, 30.3% vs. 13.0% (P = 0.0241); and at 17p13.3, 30.4% vs. 16.2% (P = 0.0243). Combined losses at 3p25.1 and 17p13.3 increased the predicted postoperative mortality risk by a factor of 4.9 (5-year mortality rate of 38.2% vs. 8.0%, P = 0.0006), and combined losses at 3p25.1 and 13q12 raised the predicted postoperative mortality risks by a factor of 2.9 (34.7% vs. 12.7%, P = 0.0441). These data indicate that loss of heterozygosity (LOH) at any one or a pair of loci at 3p25.1, 13q12, or 17p13.3 is a significant predictor of postoperative mortality for breast-cancer patients.

Adult↗
PubMed2001

Allelic losses of loci at 3p25.1, 8p22, 13q12, 17p13.3, and 22q13 correlate with postoperative recurrence in breast cancer.

We previously defined 18 chromosomal regions in which frequent allelic losses were observed in breast cancers (T. Sato et al., Cancer RES:, 50: 7184-7189, 1990; Y. Harada et al., Cancer (PHILA:), 74: 2281-2286, 1994; I. Ito et al., BR: J. Cancer, 71: 438-441, 1995; K. Tsukamoto et al., Cancer (PHILA:), 78: 1929-1934, 1996; S. Matsumoto et al., Genes Chromosomes Cancer, 20: 268-274, 1997; T. Yokota et al., JPN: J. Cancer RES:, 88: 959-964, 1997; K. Tsukamoto et al., Cancer (PHILA:), 82: 317-322, 1998; A. Iida et al., Genes Chromosomes Cancer, 21: 108-112, 1998; K. Fukino et al., Genes Chromosomes Cancer, 24: 345-350, 1999; T. Yokota et al., Cancer (PHILA:), 85: 447-452, 1999; Y. Utada et al., JPN: J. Cancer RES:, 91: 293-300, 2000). To identify specific allelic losses that might correlate with postoperative recurrence, we examined tumors from a cohort of 504 breast cancer patients, who were followed clinically for 5 years postoperatively, for allelic losses of 18 microsatellite markers. Patients whose tumors had lost an allele at 3p25.1, 8p22, 13q12, 17p13.3, or 22q13 had significantly higher risks of recurrence than those whose tumors retained both alleles at those loci; at 3p25.1, the 5-year recurrence rate was 27% among patients with losses versus 18% with retention (P = 0.0131); at 8p22, 27% versus 14% (P = 0.0129); at 13q12, 28% versus 15% (P = 0.0109); at 17p13.3, 27% versus 20% (P = 0.0482); and at 22q13, 29% versus 20% (P = 0.0477). These data indicate that loss of heterozygosity at any one of these five specific loci is a significant predictor of postoperative recurrence among patients who have undergone surgery for breast cancer. These allelic losses can serve as negative prognostic indicators to guide postoperative management of patients.

Adult↗
PubMed2000

A proposal for the histopathological diagnosis of ductal carcinoma in situ of the breast.

BACKGROUND: As the incidence of ductal carcinoma in situ (DCIS) is increasing, it is necessary to make a guideline for the pathological examination and diagnosis of DCIS, by creating criteria based on clinical and biological aspects of the disease. METHOD: We collected biopsy specimens originally diagnosed as benign lesions, from patients who subsequently developed invasive carcinoma in the ipsilateral breast. The histology of the biopsy specimens was re-evaluated principally according to the 1995 Philadelphia Consensus on DCIS. Histopathological agreement on each biopsy specimen was made by the JBCS Study Group members under a multiviewer microscope. In the course of making conclusive agreements among the pathologists, we developed a consensus for the histopathological diagnosis of DCIS, especially non-comedo types. RESULTS: DCIS is defined as a carcinoma of ductal epithelial origin, without any evidence of stromal invasion. It is necessary to note the methods of pathologic examination required to diagnose DCIS. Stromal invasion is an important prognostic factor, and should be diagnosed with caution. Classification of proliferative ductal lesions as benign or malignant (DCIS), the subtype of DCIS (nuclear grade, architecture, and necrosis), and the histological grading of DCIS are proposed and recommended. CONCLUSION: Although we have made a new proposal according to current concepts, there are still several unresolved problems. Thus further examination and modification will be necessary in the future.

Breast Neoplasms↗
PubMed2000

Surgery for ductal carcinoma in situ.

BACKGROUND: Ductal carcinomas in situ (DCIS) are sometimes treated too aggressively by surgery. We discuss minimal invasive surgery for DCIS on the basis of our experience at the Cancer Institute Hospital in Tokyo. METHODS: We performed surgery for 667 cases of DCIS between 1987 to 1998. This twelve year period we divided into three periods; 1987-1990,1991-1994, and 1995-1998. RESULTS: DCIS comprised 10% of all breast cancers, and tended to increase in incidence over time. The number of minimally invasive procedures such as breast conserving treatment (BCT), surgery without axillary dissection, and day surgery increased in later periods. In BCT for DCIS the surgical margin status is the most important factor, the rate of negative surgical margins was higher in DCIS than invasive cancer, and especially high in cases of mammographically detected nonpalpable cancer, the incidence of which is increasing yearly. The outcome of the 667 cases was very good. No distant metastases were observed, and the incidence of ipsilateral breast cancer(including second primary cancer) in these cases was 5% CONCLUSIONS: Because small cancers, including nonpalpable cases, will be detected more frequently, minimal invasive surgery will become more common for DCIS.

Axilla↗
PubMed2000

Mammographic and clinicopathological features of mucinous carcinoma of the breast.

BACKGROUND: We attempted to improve the effectiveness of diagnostic techniques in mammographic imaging of mucinous carcinoma of the breast by defining the characteristics of mammographic images and investigating correlations between these images and various clinicopathological findings. METHODS: Clinicopathological investigations of 92 lesions in 90 cases of mucinous carcinoma of the breast were made. Mammography demonstrated 80 lesions with identical tumor shadow characteristics and these were divided into three patterns, circumscribed, indistinct and blended. Correlations between clinicopathological findings and mammographic images were investigated. RESULTS: Patients with mucinous carcinoma of the breast usually present with a palpable mass. The lymph node metastasis rate in this study was low and prognosis in the early postoperative period was satisfactory. On mammograms, the circumscribed pattern was the most frequent. The investigation of the correlation between histological sub-type and mammographic pattern showed a high percentage of pure type lesions exhibited in the circumscribed pattern while those of mixed histologic type often showed the indistinct pattern. Calcification frequency demonstrated on mammography was 75% for the indistinct and mixed patterns, and approximately 50% for the circumscribed pattern. A high rate of calcification seen outside the tumor shadow suggested a high frequency of invasion and the spread of cancer to neighboring tissues. The circumscribed pattern was least frequently associated with lymph node metastasis, followed by the indistinct and blended patterns in that order. CONCLUSION: Investigation of clinicopathological factors and mammographic findings in mucinous carcinoma of the breast suggests that mammography provides clinically valuable information for the treatment of this disease. These findings indicate the importance of careful mammographic observation at the time of diagnosis.

Adenocarcinoma, Mucinous↗
PubMed2000

Identification of Rad51 alteration in patients with bilateral breast cancer.

The human Rad51 gene, HsRAD51, is a homolog of RecA of Escherichia coli and functions in recombination and DNA repair. BRCA1 and BRCA2 proteins form a complex with Rad51, and these genes are thought to participate in a common DNA damage response pathway associated with the activation of homologous recombination and double-strand break repair. Additionally, we have shown that the pattern of northern blot analysis of the RadS gene is closely similar to those of the BRCA1 and BRCA2 genes. It is therefore possible that alterations of the Rad51 gene may be involved in the development of hereditary breast cancer. To investigate this possibility, we screened Japanese patients with hereditary breast cancer for Rad51 mutations and found a single alteration in exon 6. This was determined to be present in the germline in two patients with bilateral breast cancer, one with synchronous bilateral breast cancer and the other with synchronous bilateral multiple breast cancer. In both patients, blood DNAs showed a G-to-A transition in the second nucleotide of codon 150, which results in the substitution of glutamine for arginine. As this alteration was not present in any patients with breast or colon cancer examined, we assume that this missense alteration is likely to be a disease-causing mutation.

Blotting, Northern↗